Evaluating the function of hippocampal subregions with high-resolution MRIin Alzheimer's disease and aging

Memory ability declines in older age groups. There is a growing list of phy siological processes that target the hippocampal formation in an age-relate d fashion, and some might underlie the hippocampal component of memory decl ine. The hippocampal formation is comprised of separate subregions, and phy siological processes differentially target these subregions. The ability to evaluate the functional integrity of individual subregions-performing subr egional analysis-is a major clinical goal since it can aid in the diagnosis of memory decline, as well as in elucidating mechanisms of disease and tes ting potential interventions. Because of its superior spatial resolution, m agnetic resonance imaging (MRI) is best suited to accomplish this goal. Des pite limited success, most functional MRI (fMRI) protocols have difficulty in performing complete subregional analysis of the hippocampal formation. H ere we address sources of difficulty by (1) generating T2*-weighted maps of the hippocampal formation with sub-millimeter resolution; and (2) by adapt ing an approach used by animal investigators to identify the hippocampal su bregions using anatomical landmarks. The protocol is tested in patients wit h Alzheimer's disease and in healthy controls, in an effort to determine wh ether it can detect neuronal dysfunction. Results showed diminished signal in the hippocampal formation of patients with Alzheimer's disease (AD) comp ared to controls, and multivariate analysis showed that this difference was most prominent in the entorhinal cortex. The protocol can be used to perfo rm subregional analysis of the hippocampal formation. Testing the protocol in other clinical populations is needed to demonstrate its efficacy in eval uating the neuronal integrity of all hippocampal subregions. Microsc. Res. Tech. 51:101-108, 2000, (C) 2000 Wiley-Liss, Inc.